Citations 2
Dose-dependent white matter changes associated with repetitive head impacts in former American football players
Arciniega, Hector , Wickham, Alana, Szekely, Brian, Kim, Nicholas, Cho, Kang I, Carrington, Holly, Knyazhanskaya, Evdokiya , John, Omar , Jung, Leonard , Breedlove, Katherine M. , Mirmajlesi, Anya S, Stearns, Jared, Rushmore, R Jarrett, Daneshvar, Daniel H, Wiegand, Tim L T, Billah, Tashrif , Pasternak, Ofer, Cetin-Karayumak, Suheyla, Rathi, Yogesh, Coleman, Michael J, Bernick, Charles, Balcer, Laura J, Im, Brian , Datta, Shae , Alosco, Michael L. , Lin, Alexander P, Cummings, Jeffrey L, Reiman, Eric M, Stern, Robert A, Shenton, Martha E, Bouix, Sylvain, Su, Yi, Chen, Kewei, Protas, Hillary, Boker, Connie, Au, Rhoda, Cantu, Robert C, Farrer, Lindsay, Helm, Robert, Katz, Douglas I, Kowall, Neil, Mez, Jesse, Mercier, Gustavo, Otis, James, Weller, Jason, Simkin, Irene, Andino, Alondra, Conneely, Shannon, Diamond, Courtney, Fagle, Tessa, Haller, Olivia, Hunt, Tennyson, Gullotti, Nicole, Mariani, Megan, Mayville, Brian, McLaughlin, Kathleen, Nanna, Mary, Platt, Taylor, Rice, Fiona, Sestak, Madison, McClean, Michael, Tripodis, Yorghos, Annis, Douglas, Chaisson, Christine, Dixon, Diane, Finney, Carolyn, Gallagher, Kerrin, Hartlage, Kaitlin , Lu, Jun, Martin, Brett, Ojo, Emmanuel, Palmisano, Joseph N, Pine, Brittany, Ramachandran, Janani, Fitzsimmons, Jennifer, Arcinieago, Hector, Bonke, Elena, Coello, Eduardo , Jung, Leonhard, Liao, Huijun, Loy, Maria, Rizzoni, Elizabeth, Schultz, Vivian , Silva, Annelise, Vessey, Brynn, Banks, Sarah, Miller, Jason, Ritter, Aaron , Sabbagh, Marwan, Cruz, Raelynn de la, Durant, Jan, Golceker, Morgan, Harmon, Nicolette, Kaylegian, Kaeson, Long, Rachelle, Nance, Christin, Sandoval, Priscilla, Serrano, Andrew, Dodick, David W, Geda, Yonas, Wethe, Jennifer V, Falk, Bryce, Duffy, Amy, Howard, Marci, Montague, Michelle , Osgood, Thomas, Babcock, Debra, Bellgowan, Patrick, Balcer, Laura, Barr, William, GOLDBERG, JUDITH, Wisniewski, Thomas, Kirov, Ivan, Lui, Yvonne, Marmar, Charles, Hasanaj, Lisena, Serrano, Liliana , Al-Kharafi, Alhassan, George, Allan, Martin, Sammie, Riley, Edward, Runge, William, Peskind, Elaine R. , Colasurdo, Elizabeth , Marcus, Daniel S, Gurney, Jenny , Greenwald, Richard, Johnson, Keith A, Wethe, Jennifer V. , Wiegand, Tim L. T. , Jung, Leonard B , Breedlove, Katherine , Stearns, Jared , Adler, C H , Alosco, Michael L , Koerte, Inga K , Wethe, Jennifer V , Arciniega, Hector , Kim, Nicholas , Carrington, Holly , Rushmore, R. Jarrett , Daneshvar, Daniel H. , Pasternak, Ofer , Karayumak, Suheyla Cetin , Rathi, Yogesh , Coleman, Michael J. , Adler, Charles H. , Bernick, Charles , Balcer, Laura J. , Reiman, Eric M. , Shenton, Martha E. , Bouix, Sylvain , Protas, Hillary , Cantu, Robert C. , Katz, Douglas I. , Mez, Jesse , Weller, Jason , Fagle, Tessa, Mariani, Megan, McLaughlin, Kathleen , Pulukuri, Surya Vamsi , Sestak, Madison, McClean, Michael D , Tripodis, Yorghos , Annis, Douglas, Finney, Carolyn, Palmisano, Joseph , Pine, Brittany, Ramachandran, Janani , Bonke, Elena M. , Liao, Huijun, II, Robert W. Turner , Marek, Kenneth , Dodick, David W. , Geda, Yonas E. , Howard, Marci, Montague, Michelle, Babcock, Debra, Bellgowan, Patrick S.F. , Barr, William , Kirov, Ivan, George, Allan, Colasurdo, Elizabeth A. , Marcus, Daniel S., Johnson, Keith A.
Brain Communications | May 29, 2026 | Volume: 8 | Issue: 3 | Pages: No page available
Abstract Repetitive head impacts sustained during American football have been associated with neuropathological changes such as white matter shear injuries. However, the impact of specific factors, such as age of first exposure and cumulative head impact burden, on white matter integrity remains unclear. This study investigated in vivo white matter microstructural changes using diffusion tensor imaging and tract-based spatial statistics in 165 male former American football players (mean age 57.3 years, range 45–74) and 52 unexposed asymptomatic male controls (mean age 59.4 years, range 45–74) in the DIAGNOSE CTE Research Project. Compared to controls, former football players exhibited significantly higher fractional anisotropy (FA) in 1.97% of the white matter skeleton (1552 voxels; Cohen’s d = 0.587) and higher tissue-corrected FA (FAt) in 1.48% of the white matter skeleton (1004 voxels; Cohen’s d = 0.616). No significant differences were observed for mean diffusivity, axial diffusivity, radial diffusivity, or free water between football players and controls. Among football players, there were no significant differences in the white matter microstructure between players diagnosed with traumatic encephalopathy syndrome and those without the diagnosis. Lower FA was significantly associated with older age (P < 0.00001) and an earlier age of first exposure to tackle football (P < 0.01), while lower FAt was associated with greater cumulative head impact burden, specifically higher linear acceleration (P < 0.04) and rotational force (P < 0.02). This study highlights the influential role of exposure factors on white matter microstructure in former American football players, as well as the utility of diffusion tensor imaging to aid in characterizing the long-term effects of repetitive head impacts in contact sport athletes.
Sulcal morphology in former American football players
Jung, Leonard , Mirmajlesi, Anya S, Stearns, J. W. , Breedlove, Katherine M. , John, Omar , Kim, Nicholas , Wickham, Alana, Protas, Hillary , Baucom, Zachary, Tuz‐Zahra, Fatima , Wiegand, Tim L. T. , Billah, Tashrif , Pasternak, Ofer, Im, Brian , Datta, Shae , Bernick, Charles , Balcer, Laura J. , Alosco, Michael L. , Lin, Alexander , Cummings, Jeffrey L., Reiman, Eric M. , Arciniega, Hector , Boker, Connie, Kowall, Neil W. , Otis, James , Weller, Jason , Simkin, Irene, Andino, Alondra, Diamond, Courtney , Fagle, Tessa, Haller, Olivia, Hunt, Tennyson, Gullotti, Nicole, Mariani, Megan, Mayville, Brian, McLaughlin, Kathleen , Nanna, Mary, Platt, Taylor, Rice, Fiona, Sestak, Madison, Annis, Douglas S. , Dixon, Diane, Finney, Carolyn, Gallagher, Kerrin, Hartlage, Kaitlin , Martin, Brett, Palmisano, Joseph , Pine, Brittany, Fitzsimmons, Jennifer, Pasternak, Ofer , Arcinieago, Hector, Coello, Eduardo , Coleman, Michael J. , Jung, Leonhard, Liao, Huijun, Loy, Maria, Rizzoni, Elizabeth, Schultz, Vivian , Silva, Annelise, Vessey, Brynn, Banks, Sarah J. , Ritter, Aaron, Cruz, Raelynn de la, Durant, Jan, Golceker, Morgan, Harmon, Nicolette, Kaylegian, Kaeson, Long, Rachelle, Nance, Christin, Sandoval, Priscilla, Serrano, Andrew, Falk, Bryce W., Duffy, Amy, Howard, Marci, Montague, Michelle , Osgood, Thomas, Babcock, Debra, Marmar, Charles R. , Hasanaj, Lisena, Serrano, Liliana , Al-Kharafi, Alhassan, George, Allan , Martin, Sammie, Runge, William, Peskind, Elaine R. , Colasurdo, Elizabeth A. , Marcus, Daniel S., Gurney, Jenny , Greenwald, Richard M., Johnson, Keith A. , Jung, Leonard B , Stearns, Jared , Breedlove, Katherine , Tripodis, Yorghos , Adler, C H , Alosco, Michael L , Koerte, Inga K , Arciniega, Hector , Su, Yi , Tripodis, Yorghos , Daneshvar, Daniel H. , Heller, Carina , Coleman, Michael , Adler, Charles H. , Stern, Robert A. , Shenton, Martha E. , Bouix, Sylvain , Chen, Kewei , Au, Rhoda , Cantu, Robert C. , Farrer, Lindsay A. , Helm, Robert H. , Katz, Douglas I. , Mez, Jesse , Mercier, Gustavo , Conneely, Shannon E. , Diamond, Courtney, Pulukuri, Surya Vamsi , McClean, Michael D , Annis, Douglas, Chaisson, Christine E. , Finney, Carolyn, Lü, Jun , Ojo, Emmanuel, Ramachandran, Janani , Bonke, Elena M. , Miller, Jason Rafe , Sabbagh, Marwan Noel , II, Robert W. Turner , Marek, Kenneth , Dodick, David W. , Geda, Yonas E. , Wethe, Jennifer V. , Falk, Bryce, Montague, Michelle, Bellgowan, Patrick S.F. , Barr, William , Goldberg, Judith D. , Wısnıewskı, Thomas , Kirov, Ivan I. , Lui, Yvonne W. , George, Allan, Riley, Edward P. , Cummings, Jeffrey L.
Brain Communications | September 9, 2025 | Volume: 7 | Issue: 5 | Pages: No page available
Abstract Repetitive head impacts are associated with structural brain changes and an increased risk for chronic traumatic encephalopathy, a progressive neurodegenerative disease that can only be diagnosed after death. Chronic traumatic encephalopathy is defined by the abnormal accumulation of phosphorylated tau protein, particularly at the depths of the superior frontal sulci, suggesting that sulcal morphology may serve as a relevant structural biomarker. Contact sport athletes, such as former football players, are at elevated risk due to their prolonged exposure to repetitive head impacts. Cortical atrophy linked to underlying tau accumulation may result in shallower and wider sulci, potentially making sulcal morphology an imaging marker for identifying individuals at risk for this disease. This study investigated sulcal morphological differences in former football players and examined associations with age, football-related exposure, clinical diagnosis of traumatic encephalopathy syndrome, levels of certainty for chronic traumatic encephalopathy pathology, neuropsychological performance, and positron emission tomography imaging using flortaucipir. We analysed structural magnetic resonance imaging data from 169 male former football players (mean age 57.2 (8.2) years, range 45–74) and 54 age-matched, unexposed asymptomatic male controls (mean age 59.4 (8.5) years, range 45–74). Sulcal depth and width were quantified using the CalcSulc, focusing on two regions in each hemisphere commonly affected by chronic traumatic encephalopathy pathology: the superior frontal and occipitotemporal sulci. Generalized least squares models were used to assess group differences and interactions with age and football exposure variables, including age of first exposure, total years played, and cumulative head impact exposure. An analysis of covariance evaluated relationships between sulcal morphology, clinical measures, and flortaucipir uptake, adjusting for age, race, body mass index, education, imaging site, apolipoprotein E4 status, and total intracranial volume. Former football players demonstrated significantly shallower sulcal depth in the left superior frontal sulcus compared to unexposed controls. Earlier age of first exposure and longer football careers were associated with greater widening of the left occipitotemporal sulcus. Higher cumulative head impact exposure was linked to reduced sulcal depth in the left superior frontal region. However, sulcal morphology was not associated with clinical diagnosis, levels of certainty, neuropsychological test performance, or flortaucipir imaging. These findings suggest that sulcal morphology may reflect cumulative exposure to repetitive head impacts, particularly in brain regions vulnerable to chronic traumatic encephalopathy pathology. Future ante- and post-mortem validation studies are needed to determine whether sulcal morphology can serve as a reliable in vivo biomarker of risk.